Nature structural & molecular biology最新文献_第6页

Structural basis for translational control by the human 48S initiation complex 人类 48S 启动复合体控制翻译的结构基础

Nature structural & molecular biology Pub Date : 2024-09-17 DOI: 10.1038/s41594-024-01378-4

Valentyn Petrychenko, Sung-Hui Yi, David Liedtke, Bee-Zen Peng, Marina V. Rodnina, Niels Fischer

引用次数: 0

Resistance of estrogen receptor function to BET bromodomain inhibition is mediated by transcriptional coactivator cooperativity 雌激素受体功能对 BET 溴链抑制的抗性是由转录协同激活剂的合作性介导的

Nature structural & molecular biology Pub Date : 2024-09-09 DOI: 10.1038/s41594-024-01384-6

Sicong Zhang, Robert G. Roeder

{"title":"Resistance of estrogen receptor function to BET bromodomain inhibition is mediated by transcriptional coactivator cooperativity","authors":"Sicong Zhang, Robert G. Roeder","doi":"10.1038/s41594-024-01384-6","DOIUrl":"https://doi.org/10.1038/s41594-024-01384-6","url":null,"abstract":"The bromodomain and extraterminal domain (BET) family of proteins are critical chromatin readers that bind to acetylated histones through their bromodomains to activate transcription. Here, we reveal that bromodomain inhibition fails to repress oncogenic targets of estrogen receptor because of an intrinsic transcriptional mechanism. While bromodomains are necessary for the transcription of many genes, bromodomain-containing protein 4 (BRD4) binds to estrogen receptor binding sites and activates transcription of critical oncogenes such as MYC, independently of its bromodomains. BRD4 associates with the Mediator complex and disruption of Mediator reduces BRD4’s enhancer occupancy. Profiling changes of the post-initiation RNA polymerase II (Pol II)-associated factors revealed that BET proteins regulate interactions between Pol II and elongation factors SPT5, SPT6 and the polymerase-associated factor 1 complex, which associate with BET proteins independently of their bromodomains and mediate their transcription elongation effect. Our findings highlight the importance of bromodomain-independent functions and interactions of BET proteins in the development of future therapeutic strategies.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pseudouridine guides germline small RNA transport and epigenetic inheritance 伪尿嘧啶引导种系小 RNA 运输和表观遗传

Nature structural & molecular biology Pub Date : 2024-09-06 DOI: 10.1038/s41594-024-01392-6

Rowan P. Herridge, Jakub Dolata, Valentina Migliori, Cristiane de Santis Alves, Filipe Borges, Andrea J. Schorn, Frédéric van Ex, Ann Lin, Mateusz Bajczyk, Jean-Sebastien Parent, Tommaso Leonardi, Alan Hendrick, Tony Kouzarides, Robert A. Martienssen

{"title":"Pseudouridine guides germline small RNA transport and epigenetic inheritance","authors":"Rowan P. Herridge, Jakub Dolata, Valentina Migliori, Cristiane de Santis Alves, Filipe Borges, Andrea J. Schorn, Frédéric van Ex, Ann Lin, Mateusz Bajczyk, Jean-Sebastien Parent, Tommaso Leonardi, Alan Hendrick, Tony Kouzarides, Robert A. Martienssen","doi":"10.1038/s41594-024-01392-6","DOIUrl":"https://doi.org/10.1038/s41594-024-01392-6","url":null,"abstract":"Developmental epigenetic modifications in plants and animals are mostly reset during gamete formation but some are inherited from the germline. Small RNAs guide these epigenetic modifications but how inherited small RNAs are distinguished in plants and animals is unknown. Pseudouridine (Ψ) is the most abundant RNA modification but has not been explored in small RNAs. Here, we develop assays to detect Ψ in short RNA sequences, demonstrating its presence in mouse and Arabidopsis microRNAs. Germline small RNAs, namely epigenetically activated small interfering RNAs (easiRNAs) in Arabidopsis pollen and Piwi-interacting RNAs in mouse testes, are enriched for Ψ. In pollen, pseudouridylated easiRNAs are transported to sperm cells from the vegetative nucleus, and PAUSED/HEN5 (PSD), the plant homolog of Exportin-t, interacts genetically with Ψ and is required for this transport. We further show that Exportin-t is required for the triploid block: small RNA dosage-dependent seed lethality that is epigenetically inherited from pollen. Thus, Ψ has a conserved role in marking inherited small RNAs in the germline.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"380 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exocyst stimulates multiple steps of exocytic SNARE complex assembly and vesicle fusion 外囊刺激外细胞 SNARE 复合物组装和囊泡融合的多个步骤

Nature structural & molecular biology Pub Date : 2024-09-06 DOI: 10.1038/s41594-024-01388-2

Chanwoo Lee, Dante Lepore, Seung-Hak Lee, Tae Gyun Kim, Natasha Buwa, Jongchan Lee, Mary Munson, Tae-Young Yoon

{"title":"Exocyst stimulates multiple steps of exocytic SNARE complex assembly and vesicle fusion","authors":"Chanwoo Lee, Dante Lepore, Seung-Hak Lee, Tae Gyun Kim, Natasha Buwa, Jongchan Lee, Mary Munson, Tae-Young Yoon","doi":"10.1038/s41594-024-01388-2","DOIUrl":"https://doi.org/10.1038/s41594-024-01388-2","url":null,"abstract":"Exocyst is a large multisubunit tethering complex essential for targeting and fusion of secretory vesicles in eukaryotic cells. Although the assembled exocyst complex has been proposed to tether vesicles to the plasma membrane and activate soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) for membrane fusion, the key biochemical steps that exocyst stimulates in SNARE-mediated fusion are undetermined. Here we use a combination of single-molecule and bulk fluorescence assays to investigate the roles of purified octameric yeast exocyst complexes in a reconstituted yeast exocytic SNARE assembly and vesicle fusion system. Exocyst had stimulatory roles in multiple distinct steps ranging from SNARE protein activation to binary and ternary complex assembly. Importantly, exocyst had a downstream role in driving membrane fusion and full content mixing of vesicle lumens. Our data suggest that exocyst provides extensive chaperoning functions across the entire process of SNARE complex assembly and fusion, thereby governing exocytosis at multiple steps.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Distinct stabilization of the human T cell leukemia virus type 1 immature Gag lattice 人类 T 细胞白血病病毒 1 型未成熟 Gag 网格的独特稳定性

Nature structural & molecular biology Pub Date : 2024-09-06 DOI: 10.1038/s41594-024-01390-8

Martin Obr, Mathias Percipalle, Darya Chernikova, Huixin Yang, Andreas Thader, Gergely Pinke, Dario Porley, Louis M. Mansky, Robert A. Dick, Florian K. M. Schur

引用次数: 0

Shieldin and CST co-orchestrate DNA polymerase-dependent tailed-end joining reactions independently of 53BP1-governed repair pathway choice Shieldin 和 CST 共同协调 DNA 聚合酶依赖性尾端连接反应，与 53BP1 主导的修复途径选择无关

Nature structural & molecular biology Pub Date : 2024-09-03 DOI: 10.1038/s41594-024-01381-9

Ashleigh King, Pia I. Reichl, Jean S. Metson, Robert Parker, Daniella Munro, Catarina Oliveira, Lucia Sommerova, Jordan R. Becker, Daniel Biggs, Chris Preece, Benjamin Davies, J. Ross Chapman

{"title":"Shieldin and CST co-orchestrate DNA polymerase-dependent tailed-end joining reactions independently of 53BP1-governed repair pathway choice","authors":"Ashleigh King, Pia I. Reichl, Jean S. Metson, Robert Parker, Daniella Munro, Catarina Oliveira, Lucia Sommerova, Jordan R. Becker, Daniel Biggs, Chris Preece, Benjamin Davies, J. Ross Chapman","doi":"10.1038/s41594-024-01381-9","DOIUrl":"https://doi.org/10.1038/s41594-024-01381-9","url":null,"abstract":"Tumor suppressor p53-binding protein 1 (53BP1) regulates DNA end joining in lymphocytes, diversifying immune antigen receptors. This involves nucleosome-bound 53BP1 at DNA double-stranded breaks (DSBs) recruiting Rap1-interacting factor 1 homolog (RIF1) and shieldin, a poorly understood DNA-binding complex. The 53BP1–RIF1–shieldin axis is pathological in BRCA1-mutated cancers, blocking homologous recombination (HR) and driving illegitimate nonhomologous end joining (NHEJ). However, how this axis regulates DNA end joining and HR suppression remains unresolved. We investigated shieldin and its interplay with the Ctc1–Stn1–Ten1 (CST) complex, which was recently implicated downstream of 53BP1. Immunophenotypically, mice lacking shieldin or CST are equivalent, with class-switch recombination coreliant on both complexes. Ataxia-telangiectasia mutated kinase-dependent DNA damage signaling underpins this cooperation, inducing physical interactions between these complexes that reveal shieldin as a DSB-responsive CST adaptor. Furthermore, DNA polymerase ζ functions downstream of shieldin, establishing DNA fill-in synthesis as the physiological function of shieldin–CST. Lastly, we demonstrate that 53BP1 suppresses HR and promotes NHEJ in BRCA1-deficient mice and cells independently of shieldin. These findings showcase the versatility of the 53BP1 pathway, achieved through the collaboration of chromatin-bound 53BP1 complexes and DNA end-processing effector proteins.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural insight into synergistic activation of human 3-methylcrotonyl-CoA carboxylase 从结构上洞察人类 3-甲基巴豆酰-CoA羧化酶的协同激活作用

Nature structural & molecular biology Pub Date : 2024-09-02 DOI: 10.1038/s41594-024-01379-3

Jiayue Su, Xuyang Tian, Hang Cheng, Desheng Liu, Ziyi Wang, Shan Sun, Hong-Wei Wang, Sen-Fang Sui

引用次数: 0

Structural basis for lipid transfer by the ATG2A–ATG9A complex ATG2A-ATG9A 复合物脂质转移的结构基础

Nature structural & molecular biology Pub Date : 2024-08-22 DOI: 10.1038/s41594-024-01376-6

Yang Wang, Selma Dahmane, Rujuan Ti, Xinyi Mai, Lizhe Zhu, Lars-Anders Carlson, Goran Stjepanovic

{"title":"Structural basis for lipid transfer by the ATG2A–ATG9A complex","authors":"Yang Wang, Selma Dahmane, Rujuan Ti, Xinyi Mai, Lizhe Zhu, Lars-Anders Carlson, Goran Stjepanovic","doi":"10.1038/s41594-024-01376-6","DOIUrl":"https://doi.org/10.1038/s41594-024-01376-6","url":null,"abstract":"Autophagy is characterized by the formation of double-membrane vesicles called autophagosomes. Autophagy-related proteins (ATGs) 2A and 9A have an essential role in autophagy by mediating lipid transfer and re-equilibration between membranes for autophagosome formation. Here we report the cryo-electron microscopy structures of human ATG2A in complex with WD-repeat protein interacting with phosphoinositides 4 (WIPI4) at 3.2 Å and the ATG2A–WIPI4–ATG9A complex at 7 Å global resolution. On the basis of molecular dynamics simulations, we propose a mechanism of lipid extraction from the donor membranes. Our analysis revealed 3:1 stoichiometry of the ATG9A–ATG2A complex, directly aligning the ATG9A lateral pore with ATG2A lipid transfer cavity, and an interaction of the ATG9A trimer with both the N-terminal and the C-terminal tip of rod-shaped ATG2A. Cryo-electron tomography of ATG2A liposome-binding states showed that ATG2A tethers lipid vesicles at different orientations. In summary, this study provides a molecular basis for the growth of the phagophore membrane and lends structural insights into spatially coupled lipid transport and re-equilibration during autophagosome formation.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142021861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural plasticity of bacterial ESCRT-III protein PspA in higher-order assemblies 细菌 ESCRT-III 蛋白 PspA 在高阶组装中的结构可塑性

Nature structural & molecular biology Pub Date : 2024-08-16 DOI: 10.1038/s41594-024-01359-7

Benedikt Junglas, Esther Hudina, Philipp Schönnenbeck, Ilona Ritter, Anja Heddier, Beatrix Santiago-Schübel, Pitter F. Huesgen, Dirk Schneider, Carsten Sachse

{"title":"Structural plasticity of bacterial ESCRT-III protein PspA in higher-order assemblies","authors":"Benedikt Junglas, Esther Hudina, Philipp Schönnenbeck, Ilona Ritter, Anja Heddier, Beatrix Santiago-Schübel, Pitter F. Huesgen, Dirk Schneider, Carsten Sachse","doi":"10.1038/s41594-024-01359-7","DOIUrl":"https://doi.org/10.1038/s41594-024-01359-7","url":null,"abstract":"Eukaryotic members of the endosome sorting complex required for transport-III (ESCRT-III) family have been shown to form diverse higher-order assemblies. The bacterial phage shock protein A (PspA) has been identified as a member of the ESCRT-III superfamily, and PspA homo-oligomerizes to form rod-shaped assemblies. As observed for eukaryotic ESCRT-III, PspA forms tubular assemblies of varying diameters. Using electron cryo-electron microscopy, we determined 61 Synechocystis PspA structures and observed in molecular detail how the structural plasticity of PspA rods is mediated by conformational changes at three hinge regions in the monomer and by the fixed and changing molecular contacts between protomers. Moreover, we reduced and increased the structural plasticity of PspA rods by removing the loop connecting helices α3/α4 and the addition of nucleotides, respectively. Based on our analysis of PspA-mediated membrane remodeling, we suggest that the observed mode of structural plasticity is a prerequisite for the biological function of ESCRT-III members.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Topoisomerase-modulated genome-wide DNA supercoiling domains colocalize with nuclear compartments and regulate human gene expression 拓扑异构酶调控的全基因组DNA超卷曲结构域与核分区共定位并调控人类基因表达

Nature structural & molecular biology Pub Date : 2024-08-16 DOI: 10.1038/s41594-024-01377-5

Qian Yao, Linying Zhu, Zhen Shi, Subhadra Banerjee, Chongyi Chen

{"title":"Topoisomerase-modulated genome-wide DNA supercoiling domains colocalize with nuclear compartments and regulate human gene expression","authors":"Qian Yao, Linying Zhu, Zhen Shi, Subhadra Banerjee, Chongyi Chen","doi":"10.1038/s41594-024-01377-5","DOIUrl":"https://doi.org/10.1038/s41594-024-01377-5","url":null,"abstract":"DNA supercoiling is a biophysical feature of the double helix with a pivotal role in biological processes. However, understanding of DNA supercoiling in the chromatin remains limited. Here, we developed azide-trimethylpsoralen sequencing (ATMP-seq), a DNA supercoiling assay offering quantitative accuracy while minimizing genomic bias and background noise. Using ATMP-seq, we directly visualized transcription-dependent negative and positive twin-supercoiled domains around genes and mapped kilobase-resolution DNA supercoiling throughout the human genome. Remarkably, we discovered megabase-scale supercoiling domains (SDs) across all chromosomes that are modulated mainly by topoisomerases I and IIβ. Transcription activities, but not the consequent supercoiling accumulation in the local region, contribute to SD formation, indicating the long-range propagation of transcription-generated supercoiling. Genome-wide SDs colocalize with A/B compartments in both human and Drosophila cells but are distinct from topologically associating domains (TADs), with negative supercoiling accumulation at TAD boundaries. Furthermore, genome-wide DNA supercoiling varies between cell states and types and regulates human gene expression, underscoring the importance of supercoiling dynamics in chromatin regulation and function.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0